Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa
Lin Jin,
Mahendra P. Kashyap,
Yunjia Chen,
Jasim Khan,
Yuanyuan Guo,
Jari Q. Chen,
Madison B. Lee,
Zhiping Weng,
Allen Oak,
Prasanth Patcha,
Tiffany Mayo,
Rajesh Sinha,
Venkatram Atigadda,
Shahid M. Mukhtar,
Jessy S. Deshane,
Chander Raman,
Carly Elston,
Boni E. Elewski,
Craig A. Elmets,
Mohammad Athar
Affiliations
Lin Jin
Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Mahendra P. Kashyap
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Yunjia Chen
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jasim Khan
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Yuanyuan Guo
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jari Q. Chen
Hoover High School, Hoover, Birmingham, AL 35244, USA
Madison B. Lee
School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Zhiping Weng
Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Allen Oak
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Prasanth Patcha
Division of Plastic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Tiffany Mayo
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Rajesh Sinha
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Venkatram Atigadda
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Shahid M. Mukhtar
Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jessy S. Deshane
Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Chander Raman
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Carly Elston
Department of Dermatology and Dermatopathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Boni E. Elewski
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Craig A. Elmets
Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Mohammad Athar
Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Dermatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Corresponding author
Summary: Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5′-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.